1. Field of the Invention
The present invention relates to magnetic nanoparticles applicable in imaging, diagnosis, therapy and biomaterial separation, and more particularly to magnetic nanoparticles suitable for use as contrast agents in Magnetic Resonance Imaging and a fabrication method thereof.
2. Description of the Related Art
In the biotechnology field, magnetic nanoparticles are applicable in imaging, diagnosis, therapy, biomaterial separation and so on. It is used, for example, in imaging as a contrast agent or a tracer to enhance the imaging contrast or to trace the presence of a certain disease. Furthermore, magnetic nanoparticles are also applicable in drug delivery and cancer therapy.
Currently, a number of image analysis techniques such as Computer Topography (CT), Magnetic Resonance Imaging (MRI), and ultrasound (US) are applied in disease diagnosis. The popular analysis technique of computer topography employs an X-ray to image for example, a human body by X-ray diffraction of various tissues with various densities. In addition, a contrast agent may be added during analysis to enhance the contrast among different tissues or organs. However, the radiation of X-rays may bring undesired side effects, thus Magnetic Resonance Imaging (MRI) has been provided as an alternative analysis technique.
Magnetic resonance imaging is capable of showing selectively image several different characteristics of tissues. The level of tissue magnetization at specific signal recording times during the MR imaging cycle generally determines the brightness of a particular tissue in the MRI images. Contrast is produced when tissues do not have the same level of magnetization. There are three primary magnetic characteristics of tissue that are the source of image contrast. Two of these are associated with the longitudinal magnetization. They are proton density and T1, the longitudinal relaxation time. The third characteristic is associated with the transverse magnetization. It is T2, the transverse relaxation time.
Diagnosis of brain disorders has been markedly improved by using MRI, which can delineate detailed anatomic structures with excellent tissue contrast on T1, T2, and proton density-weighted images; however, the inherent tissue characteristics do not always produce adequate contrast for some clinical applications. The administer materials that will alter the magnetic characteristics within specific tissues or anatomical regions, and can disclose abnormal enhancement after intravenous administration of contrast agents due to brain-blood-barrier (BBB) disruption. Advanced MR imaging technique, which can detect in vivo physiological changes in human brain, such as water diffusion, blood volume and blood flow have been implemented in clinical MR scanners.
Certain materials are susceptible to magnetic field and become magnetized when located in field. The orbital electrons in the atom rather than magnetic properties of the nucleus determine the susceptibility of a material. Contrast agents used in MRI are generally based on susceptibility effects. Using dynamic susceptibility contrast technique takes the advantage of T2 signal changes during the first-pass of a bolus of contrast agents. Hemodynamic parameters can then be calculated in terms of cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT) for diagnosis in clinical.
MRI provides a non-invasive diagnosis. An MRI with contrast agent enhancement increases sensitivity and specificity of imaging in many cases particularly when relaxation times among different tissues are similar.
MRI contrast agents can be classified differently according to their magnetic properties (paramagnetic, ferromagnetic or superparamagnetic). However, current commercial MRI contrast agents employing magnetic nanoparticles have poor specificity and their contrast enhancement could be improved.
U.S. Pat. No. 5,427,767 discloses iron oxide doped with an isotope, such as, 155Gd, 156Gd, or 157Gd. Pure isotopes, however, are much higher in cost than a natural isotope mixture. Further, the doping ratio and its effect on improving magnetization or transverse relaxivity (r2) are not discussed. The core/shell structure of the disclosed is a metal core coated by an organic molecular shell.
J. Appl. Phys. Vol. 79, No. 8, page 4869-4871 discloses lanthanide and boron oxide-coated α-Fe particles. The shell of the particles comprises inner-transition metal, and further comprises boron oxide as B2O3.
Similar to U.S. Pat. No. 5,427,767, Appl. Phys. Lett. Vol. 78, No. 23, page 3651-3653 discloses a CoFe2O4 nanoparticle doped with lanthanide ions. The CoFe2O4 nanoparticles are only doped with lanthanide ions, and the lanthanide ions do not form a shell coating on the CoFe2O4 nanoparticles.